This proposal is directed towards the development of new approaches to the construction of naturally occurring substances with important biological activity. The goal of the studies that we propose herein is not the total synthesis of complex organic molecules per se, but rather the development of new strategies in synthetic chemistry which will have applications beyond the construction of a particular class of natural products. We have developed an intramolecular (2+2) photocycloaddition protocol, the intramolecular dioxolenone photocycloaddition, and have demonstrated its utility in the synthesis of compounds which cannot be otherwise prepared. We propose herein to apply this methodology to the control of absolute stereochemistry in the photochemical cyclization, and to the preparation of naturally occurring compounds with important cytotoxic properties. We also describe herein our preliminary results with a different chromophore, a vinylogous amide, which leads to the formation of nitrogen-containing ring systems. A study of the generality of this process, and its application to the synthesis of antitumor alkaloids is proposed herein. Through the studies outlined above, we hope to develop new methodology for the stereochemically-controlled formation of carbon-carbon bonds. Using readily available chiral auxiliaries, the intramolecular dioxolenone photocycloaddition offers considerable promise for achieving absolute control of stereochemistry, an important goal in modern synthetic organic chemistry. The strategy that we have outlined for the synthesis of natural products using intramolecular (2+2) photocycloadditions of dioxolenones and vinylogous amides has counterparts in the Diels-Alder reaction, cationic polyene cyclization, and arene- olefin cycloaddition. More than one carbon-carbon bond and considerable stereochemical information is generated in a single synthetic operation. The constructions of the carbon skeleta of the ingenane and clerodane diterpenes, taxusin, mesembrine, and the vinca alkaloids outlined in this proposal attest to the considerable potential for this methodology in synthesis.